This Program Project brings together a group of investigators which comprises a broad range of experimental and computational techniques in three-dimensional structure analysis for a concerted study of the fundamental aspects of protein folding and assembly. The Program will capitalize on the availability of a core facility of state-of-the-art computational, computer graphic, x-ray diffraction and NMR spectroscopy equipment. The research will approach the question of ordering of protein structure using both experimental and computational techniques applied to systems that range from peptide fragments to intact viruses. The Program represents a new and very significant undertaking within the department that will utilize the complementary strengths of the large group of principal investigators and co-investigators to approach one of the most fundamental problems in molecular biology. In Project 1, Dr. Case will use molecular dynamics simulations to study hydrogen bonding in the formation of characteristic secondary structures in peptide fragments. In parallel, Dr. Wright's group in Project VI, will explore by NMR methods the mechanism and dynamics of protein folding and assembly at the level of peptide fragments. They will study the influence of amino acid sequence on the stability of secondary structure of peptides and investigate their folding and stabilization through interactions at the surface of a folded carrier protein. At the next level of association, Dr. Stout and co-investigators in Project IV will examine possible pathways between two observed tertiary folds seen for a domain of metallothionein using high pressure crystallography as well as distance geometry and molecular mechanics. In Project V. Dr. Wilson will use x-ray crystallography coupled with immunologic data to understand the nature of protein peptide and protein-protein association required for recognition and stable complex formation. By studying a series of antibody complexes a detailed understanding of epitope organization and recognition will be gained. In Project II, Dr. Hogle will use a combination of biological characterization crystallographic studies and molecular modeling to understand the structural basis for temperature sensitivity and its dependance on sequence and structure in the poliovirus. Dr. Olson in Project III will characterize a broad range of assembled interfaces including those in viruses and antibodies using computer graphics modeling coupled with calculations of shape, electrostatic energy, hydrophobicity, and solvent contributions. By focusing on overlapping system, techniques, and questions, this Program Project will foster significant collaborative interactions which will enhance the value of each individual project.